Predection for sensitivity of gefitinib against Non-small cell lung cancer

目的：吉非替尼是一种表皮生长因子受体(EGFR，HER1/ErbB1)酪氨酸激酶的抑制剂，已显示出抗非小细胞肺癌(NSCLC)的临床活性。本研究的目的是比较HER家族(EGFR、HER2、HER3、HER4)的表达状况与EGFR基因突变和吉非替尼的临床疗效的关系。采用免疫组织化学方法(IHC)检测31例肿瘤组织中HER家族的表达，用聚合酶链式反应单链构象多态(SSCP)方法检测17例冷冻组织中EGFR基因突变。结果：EGFR阳性21例(68%)，HER2阳性24例(77%)，HER3阳性17例(55%)，HER4阳性4例(13%)。其中14例(45%)EGFR和HER2以及HER3或HER4呈三重表达。三重表达组的有效率(RR)和进展时间(TTP)显著高于其他组(RR 50vs11%；P&lt；0.05，中位TTP 4.29 vs 1.2个月；P&lt；0.05)，但与HER家族成员的个体表达状况没有差异。在17例冷冻肿瘤组织中发现6个EGFR突变(48%)。Gefitinib可联合作用于EFGR、HER2及其他HER家族成员，为选择对治疗最敏感的患者提供了一种手段。

PURPOSE : Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR, HER1/ErbB1) tyrosine kinase that has shown clinical activity against non-small-cell lung cancer (NSCLC). The aim of the present study was to compare the relationship between expression status of HER family(EGFR, HER2,HER3,HER4) and EGFR gene mutations and clinical response to gefitinib.PATIENTS AND METHODS : Lung carcinoma tissues of advanced or recurrent NSCLC patients treated with monotherapy of gefitinib were analyzed. Expressions of HER family in 31 tumors were exmined by immunohistochemistry (IHC) and EGFR gene mutations were examined in 17 frozen tissues by PCR single-strand conformation polymorphism (SSCP) analysis. The medical records were reviewed for clinical variables.RESULTS : Total positivity rates were 21 for EGFR (68%), 24 for HER2 (77%), 17 for HER3 (55%) and 4 for HER4 (13%). Fourteen of 31 (45%) demonstrated triple expression of EGFR and HER2, as well as HER3 or HER4. A significantly better response rate (RR) and time to progression (TTP) were observed for the group with the triple expression than for the other groups (RR 50 vs 11% ; P<0.05, median TTP 4.29 vs 1.2 months ; P<0.05), although no difference was found with the expression status of individual HER family members. Six EGFR mutations were found in 17 frozen tumor tissues (48%). Triple expression of HER family were present in all 6 cases with EGFR mutations and in 4 of 11 cases without mutations ; P=.011.Conclusion : Gefitinib may act on EFGR and HER2 and other HER family members in combination, providing a means for selection of patients most likely to respond to therapy.